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Stress-Induced Retrotranslocation Of Clusterin/Apoj Into The Cytosol, P Nizard, Suzanne Tetley, Y Le Drean, T Watrin, P Le Goff, Mark R. Wilson, Denis Michel
Stress-Induced Retrotranslocation Of Clusterin/Apoj Into The Cytosol, P Nizard, Suzanne Tetley, Y Le Drean, T Watrin, P Le Goff, Mark R. Wilson, Denis Michel
Mark R Wilson
Clusterin is a usually secreted glycoprotein with chaperone properties. Recently, it has been suggested that clusterin isoforms reside in the nuclear and cytosolic compartments of human cell types, where they can influence various cellular programs including DNA repair, transcription and apoptosis. Several mechanisms have been proposed to explain this atypical location, including alternative transcription initiation and alternative splicing. However none of these have been unequivocally established as occurring in live cells. Here we provide direct experimental evidence that in live intact cells, under certain stress conditions, clusterin can evade the secretion pathway and reach the cytosol. This was demonstrated using …
Clusterin Facilitates In Vivo Clearance Of Extracellular Misfolded Proteins, Amy R. Wyatt, Justin J. Yerbury, Paula Berghofer, I Greguric, Andrew Katsifis, Christopher Dobson, Mark R. Wilson
Clusterin Facilitates In Vivo Clearance Of Extracellular Misfolded Proteins, Amy R. Wyatt, Justin J. Yerbury, Paula Berghofer, I Greguric, Andrew Katsifis, Christopher Dobson, Mark R. Wilson
Mark R Wilson
The extracellular deposition of misfolded proteins is a characteristic of many debilitating age-related disorders. However, little is known about the specific mechanisms that act to suppress this process in vivo. Clusterin (CLU) is an extracellular chaperone that forms stable and soluble complexes with misfolded client proteins. Here we explore the fate of complexes formed between CLU and misfolded proteins both in vitro and in a living organism. We show that proteins injected into rats are cleared more rapidly from circulation when complexed with CLU as a result of their more efficient localisation to the liver and that this clearance is …
Clusterin Interacts With Paclitaxel And Confer Paclitaxel Resistance In Ovarian Cancer, Dong Choon Park, Seung Geun Yeo, Mark R. Wilson, Justin J. Yerbury, Joseph Kwong, William R. Welch, Yang Kyu Choi, Michael J. Birrer, Samuel C. Mok, Kwong-Kwok Wong
Clusterin Interacts With Paclitaxel And Confer Paclitaxel Resistance In Ovarian Cancer, Dong Choon Park, Seung Geun Yeo, Mark R. Wilson, Justin J. Yerbury, Joseph Kwong, William R. Welch, Yang Kyu Choi, Michael J. Birrer, Samuel C. Mok, Kwong-Kwok Wong
Mark R Wilson
Optimal debulking followed by chemotherapy is the standard treatment of managing late-stage ovarian cancer, but chemoresistance is still a major problem. In this study, we compared expression profiles of primary tumor tissue from five long-term (>8 years) and five short-term (years) ovarian cancer survivors and identified clusterin as one of the genes that were significantly up-regulated in short-term survivors. We then evaluated the prognostic significance of clusterin and its possible correlation with chemoresistance in ovarian cancer by immunohistostaining of clusterin in 62 tumor samples from patients with stage III, high-grade serous ovarian cancer. After adjusting for debulking status and …
Identification Of Human Plasma Proteins As Major Clients For The Extracellular Chaperone Clusterin, Amy R. Wyatt, Mark R. Wilson
Identification Of Human Plasma Proteins As Major Clients For The Extracellular Chaperone Clusterin, Amy R. Wyatt, Mark R. Wilson
Mark R Wilson
Clusterin (CLU) is an extracellular chaperone that is likely to play an important role in protein folding quality control. This study identified three deposition disease-associated proteins as major plasma clients for clusterin by studying CLU-client complexes formed in response to physiologically relevant stress (shear stress, similar to 36 dynes/cm(2) at 37 degrees C). Analysis of plasma samples by size exclusion chromatography indicated that (i) relative to control plasma, stressed plasma contained proportionally more soluble protein species of high molecular weight, and (ii) high molecular weight species were far more abundant when proteins purified by anti-CLU immunoaffinity chromatography from stressed plasma …